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Fritsch-Buttenberg-Wiechell Rearrangement

Fritsch-Buttenberg-Wiechell Rearrangement. Vinylcarbenoid. Vinylcarbene. A Mechanistic Odyssey in the Realm of Vinylcarbenes & Vinylcarbenoïds (Journey through the life of reactive intermediates). Leading references Knorr, R, Chem. Rev. 2004 , 104 , 3795-3849

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Fritsch-Buttenberg-Wiechell Rearrangement

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  1. Fritsch-Buttenberg-Wiechell Rearrangement Vinylcarbenoid Vinylcarbene

  2. A Mechanistic Odyssey in the Realm of Vinylcarbenes & Vinylcarbenoïds (Journey through the life of reactive intermediates) Leading references Knorr, R, Chem. Rev.2004, 104, 3795-3849 Braun, M. Angew. Chem. Int. Ed.1998, 37, 430-451

  3. Outline • General consideration about FBW rearrangement • Free vinylcarbene formation • General • From vinyl triflates • From diazoalkenes • From iodonium ylides • From vinyl halides • 3) Vinylcarbenoids formation • General considerations • Strained cycles

  4. FBW : General Discovered in 1894 by Fritsch, Buttenberg and Wiechell Retro FBW Possible in gaz phase at >650C but generaly very disfavored. Exeption : very strained alkynes

  5. Vinylcarbenes (alkylidenecarbene) caracteristics Spin multiplicity Electrophilicity/nucleophilicity Determined by examination of the [1+2] reaction of vinylcarbene with a serie of substituted styrenes. S0 state confirmed by stereochemistry of addition to double bond and theorical calculations S0 S1 T1 • = -0.75 Vinylcarbene are mildly electrophilic species Stang, P. Chem. Rev. 1978, 78, 383

  6. Vinylcarbenes (alkylidenecarbene) caracteristics Association with Metals Do not seem to have much influence. Steric effects The [1+2] addition of vinylcarbenes is sensible to hinderance on the double bond (tetrasubstitued alkenes reacts slowly)

  7. Generation of vinylcarbenes 1-Halogenoalkenes Vinyl triflates Iodonium Ylides Diazoalkenes Nitrosocarbonamides N-(aziridyl)aldimines

  8. Synthesis of vinyl triflates 1 2 3 4 Stang, P. J. Acc. Chem. Res.1978, 11, 108

  9. Deprotonation of vinyl triflates Deprotonation is effected in polar solvent at or below 0C Most used base : KOt-Bu To know if a deprotonation is at equlibrum, perform the reaction in adequate deuterated solvent and perform NMR of residual starting material Driving force to high energy carbene is probably the large pKa difference between KOt-Bu and KOTf

  10. Carbenes from vinyl triflates : Common side-products 1 via 2 Addition of nucleophilic solvents THF can act as Lewis base and add on the carbene to gives an oxonium ion that can be opened by alcohols

  11. Carbenes from vinyl triflates : Comparative studies Comparaison between [1+2] and insertion

  12. Carbenes from vinyl triflates : Comparative studies General reactivity order: H & Ph migration > [1+2] > OHinsert = SiHinsert > 1,5-CHinsert

  13. How to prove the intermediacy of carbene Like carbenes, carbenoïds can perform OH insertion and [1+2]. Witch one is the reactive species? If two precursor can lead to product directly or via a common intermediate, an identical products distribution for each is a necessary albeit not sufficient condition for the existence of the common intermediate Conclusion: Vinyl triflates probably generates free carbenes Stang, P.J.; Mangum, D.P.F.; Haak, P. J. Am. Chem. Soc.1974, 96, 4562

  14. How to prove the intermediacy of carbene, part 2! A way to prove a reaction intermediate is to generate it from at least 2 independent sources. If the reactivity of that intermediate remain the same, it is probably real. Conclusion Vinyl triflates generates free carbenes

  15. Carbenes from diazoalkenes Deprotonated diazoalkenes can be considered as nitrogen complex of carbenes Synthesis 1 Seyfert-Gilbert reagent (DAMP) 2 Peterson olefination

  16. Carbenes from diazoalkenes FBW • Similar to carbenes from vinyl trilfates • H and Ar migrate easily and the alkyne is obtained in good yield. (40 – 90%) • Exception: (destabilize d+ charge in the transition state) Side-reactions have enough time to occur. Insertion Since alkyl groups do not migrate well, OH & NH insertion reaction can occur in good yield.

  17. 1,5-CH insertion of vinylcarbenes Intramolecular 1,5-CH insertion are possible with vinylcarbenes with an appropriate chain. Competition experiments gave the following (not surprising) selectivity: Works well :o) Insertion into chiral CH occur with >99% retention The strange case of amides migration and CH insertion The problem: Like H and Ar, amides migrate very well. However, carbenes with tertiary amide do prefer 1,5-CH insertion of primary H

  18. The strange case of amides migration & CH insertion Amide group is essential! Stabilisation of radical transition state Answer comes from conformational analysis 1. Dipole minimization 2. Amide conformation 3. Rate of amide rotation is not competitive with the rate of decomposition and CH insertion

  19. Other sources of diazoalkenes & vinylcarbenes N-(aziridyl)aldimines Nitrosocarbonamides • Carbene are produced in medium yield • SM is difficult to prepare Not very appealing… Kim, S.; Cho., C. M. Tetrahedron Lett.1994, 35, 8405

  20. Carbenes from iodonium ylides Structure Stability Relatively stable if R = EWG C-I do not have a double bond character If R is not EWG, compound isn't isolable but can be generated in situ

  21. Iodonium ylides synthesis From stannylacetylenes: Good nucleophiles: Activated carbonyl, NR2, N3, PPh3, Phenoxydes, sulfonates, phosphonates, carboxylates Bad nucleophiles: Enolates, alkoxydes, RLi

  22. Iodonium ylides conformational stability Result: Z ylide form the alkyne 3.7 times faster than E ylide Conclusion: No fast equilibrium of ylides Carbene formation?

  23. Vinylic carbocation formation? • IPh is one of the best known leaving group. • 106 times better than Triflate • 1012 times better than Tosylate One way to choose between two mechanism is to perform a reaction on a chiral substrate that form an achiral intermediate according to one mechanism and not according to the other. Chiral product = No achiral intermediate Racemic product = Achiral intermediate Result: Complete retention of configuration Conclusion: No vinylic carbocation

  24. Iodonium ylides in nucleophilic medium Low [Cl-] = B is favored Medium [Cl-] = A is favored High [Cl-] = B is favored Note: For large R, ligand coupling mechanism leads to Cl insertion with retention

  25. Carbenes from 1-Halogenoalkenes Deprotonation : The Base : Base cannot be BuLi because Br-Li exchange is faster than deprotonation Bad bases = NaH, i-Pr2NEt Good bases = NaHMDS, KHMDS, KOt-Bu

  26. Competion between Carbene & Carbenoid FBW vs 1,5-CH insertion 1,5-CH insertion : primary vs secondary vs tertiary Similar ratio show that CH insertion is only performed by the carbene

  27. Summary of reactivity

  28. Half-Meeting traditional question (+ beer time) Propose a mechanism for the following transformation

  29. Half-Meeting traditional question answer (beer time is over…) Brown, R. F. C. et al.Aust. J. Chem.1974, 27, 2373

  30. Vinylcarbenoids: General Structure Li-13C coupling constant show that Li,Br carbenoïds are monomers in THF Stability Residual SM can catalyse the isomerisation via fast M-Br exchange. Boche, G.; Marsch, M.; Muller, A.; Harms, K. Angew. Chem. Int. Ed. Engl. 1993, 32, 1032 Hafner, K. Pure Appl. Chem,1990, 62, 531

  31. Vinylcarbenoids: Common side-products

  32. Mechanistic black hole Should come from the migration of CH2 without net breaking the C-Br bound. “Thus, the detailled mechanisms of both syn and anti migrations are open problems.” - R. Knorr - Erikson, K. L. J. Org. Chem.1971, 36, 1031 Samuel, S. P.; Niu, T.; Erikson, K. L. J. Am. Chem. Soc.1989, 111, 1429

  33. Strained cycle formation

  34. Expansion from 7 to 8 membered ring Usually do not occur. (Remember: alkyl groups do not migrate well…) Cyclobutyne is the smallest stable cyclic alkyne Curtin, D. Y.; Richardson, W. H. J. Am. Chem. Soc.1959, 81, 4719 Expansion from 6 to 7 membered ring Do not occur. Curtin, D. Y.; Richardson, W. H. J. Am. Chem. Soc.1959, 81, 4719

  35. Expansion from 5 to 6 membered ring Seem to occur, the cycloalkyne can be trapped with various agents Strange behavior due to high ring strain benzyne norboryne cyclohexyne 1 Benzyne

  36. Expansion from 5 to 6 membered ring 2 Norboryne

  37. Expansion from 5 to 6 membered ring 2 Cyclohexyne

  38. Expansion from 4 to 5 membered ring Seem to occur, the cycloalkyne can be trapped with various agents Still more strange behavior due to high ring strain Cyclopropyne is so strained that it can be considered as a 1,2-dicarbene (and react like so) Gilbert, J. C.; Baze, M. E. J. Am. Chem. Soc.1983, 105, 664 Bachrach, S. M.; Gilbert, J. C.; Laird, D. W. J. Am. Chem. Soc. 2001, 123, 6706

  39. Expansion from 4 to 5 membered ring, part 2 Cyclopentyne reactivity depend of the way it is generated Explanation: There must be an other intermediate. Variation of M and X on the organometallic precursor should be done as well as 13C labeling. Gilbert, J. C.; McKinley, E. G.; Hou, D-R. Tetrahedron1997, 53, 9891

  40. Expansion from 3 to 4 membered ring Do not occur. Theorical existence of cyclobutyne is controversial Jonas, V.; Böhme, M.; Frenking, G. J. Phys. Chem.1992, 96, 1640 Expansion from 2 to 3 membered ring Do not occur. “Cyclopropyne ring was calculated not to be a local minimum” –Rudolf Knorr Johnson, R. P.; Daoust, K. J. J. Am. Chem. Soc.1995, 117, 362

  41. CH insertion of carbenoïds 1,5-CH insertion are rare for vinylcarbenoïds. The corresponding carbene can never be excluded Fisher, R. H.; Baumann, M., Köbrich, G Tetrahedron Lett.1974, 1207

  42. Migration of unsaturated substituents Fienemann, H.; Köbrich, G Chem. Ber.1974, 107, 2797

  43. Carbenes vs. Carbenoids : kinetic 2 cases: At low temperature, carbenoïds are kinetically stable and can react in a plain bimolecular reaction. The carbene reacts much more faster than the carbenoid 1 2

  44. Carbenes vs. Carbenoïds : kinetic Case 1: Stable carbenoid react in a bimolecular reaction without rate-controlling intermediate Independence of the rate and MX concentration Case 2: Carbenoid is in fast equilibrium with the carbene and only the carbene react in a bimolecular reaction Decreased rate for increased MX concentration

  45. Summary of migration capability of vinylcarbenoids Small ring migration Newman, M. S.; Gromelski, S. J. J. Am. Chem. Soc.1972, 37, 3220 Heteroatom migration

  46. Summary of migration capability of vinylcarbenoids Enol ether migration Explanation OiPr destabilize the SP center in the transition state via its inductive effect (s = -0.12) even if it is a strong p-donor. Calculations show then O-iPr do not solvate the Li atom Alkoxyde migration Alkoxyde do not migrates, but helps the migration of other groups Kowalski, C. J.; Reddy, R. E. J. Org. Chem.1992, 57, 7194

  47. Summary Good migrating groups in the FBW rearrangement are H and Ar 1,5-CH insertion of vinylcarbenes & vinylcarbenoids can be a clean reaction Vinyl triflates, vinyl diazonium salts and vinyl iodonium ylides produce free vinylcarbenes 1,1-bromolithioolefins produce a mix of free carbenes and carbenoids Vinylcarbenoids are stable at low temperature Cycloalkynes can be produced in situ from vinylcarbenes & vinylcarbenoids Vinylcarbenoids behavior is mechanistically underdeveloped

  48. The End

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